These investigations are primarily directed at an assessment of the effects of immunoregulatory drugs on lymphocyte numbers and functions. Using a guinea pig model, studies have defined the effects of the in vivo administration of cyclophosphamide on mitogen-induced cellular cytotoxicity. A second study examined the in vitro activities of several cytotoxic drugs on the capacity of guinea pig lymphocytes to mediate mitogen-induced and antibody dependent cellular cytotoxicity. Additional investigations assessed the effects of pharmacologic quantities of prostaglandin E1 in murine lymphocytes and the abilities of this compound to inhibit immune complex glomerulonephritis. In the forthcoming year, several related studies will be performed in order to further define the effects of immunoregulatory compounds on lymphocytes. A major component will be directed at the cellular requirements for in vitro growth of T lymphocyte colonies in man and T and B cell colonies in mice. These assays will also be used to detect immunologic abnormalities in several clinical disorders and to measure its inhibitory effects of cytotoxic drugs. Other areas of investigation will include: 1) the immunosuppressive effects of combined plasmaphoresis and cyclophosphamide in severe, acute immune-complex disorders; 2) the potential synergistic effects as immune inhibitors of multidrug cytotoxic protocols in animal models; 3) the temporal relationship between therapy and immunostimulants.